It
is often assumed that systemic co-morbidities, such as diabetes mellitus (DM) and
hypertension (HT), are associated with a higher prevalence of glaucoma. However, there
is also a suspicion that the number of patients with systemic disorders are diagnosed with glaucoma simply because of the increased approach of these patients to
medical facilities and frequent eye checkups compared to normal, healthy populations, leading to higher rates of diagnosis. However, many landmark studies
have definitely reported a significantly increased association of co-morbid systemic disorders and glaucoma.
A
5-year cohort study was performed by Zhou et al, to analyze the association
between systemic comorbidity burden and glaucoma progression. [1] The comorbidity
burden was measured by the age-adjusted Charlson Comorbidity Index (age-CCI)
among patients attending the Cole Eye Institute in the USA. The Charlson
Comorbidity Index (CCI) is a widely used assessment tool designed to predict
long-term mortality. The objective of the study was to investigate whether higher
CCI scores are associated with worse glaucoma outcomes, specifically
progression to a more advanced stage of disease.
The
retrospective cohort study included 11,863 patients aged 18 years of age or
older diagnosed with primary open angle glaucoma, pre-glaucoma, or ocular
hypertension between 2018 and 2024 with at least 5 years of follow-up.
The
authors found that each one-point increase in the age-CCI score was associated
with a 6% increase in the odds of progression from early-stage to
moderate-stage glaucoma over the 5-year follow-up period (OR = 1.06, 95% CI:
1.04–1.09, P = 1.05×10−7). The odds of progression to moderate-stage glaucoma were
higher in males compared with females (OR = 1.32, 95% CI: 1.17–1.49, P =
4.15×10−6). Compared with white patients, the odds of progression were higher
for the black (OR = 2.09, 95% CI: 1.81–2.40, P < 2×10−16) and “other race”
(OR = 1.81, 95% CI: 1.47–2.23, P = 1.52×10−8) cohorts. Patients with private
insurance had lower odds of progression than those with public insurance (OR =
0.75, 95% CI: 0.65–0.86, P = 2.89×10−5), whereas patients with no listed
insurance had no significant difference compared with those with public
insurance. Patients with a history of one or more ophthalmic procedures or age
related macular degeneration (AMD) diagnosis had higher odds of progression
from early-stage to moderate- stage glaucoma than those without (OR = 1.33, 95%
CI: 1.17–1.51, P = 1.84×10−5; OR = 1.34, 95% CI: 1.05–1.71, P = 0.017).
Finally, each increase in prescribed glaucoma medication was associated with
88% increased odds of progression (95% CI: 1.80–1.97, P < 2×10−16).
The
study also analyzed the progression from early-stage to severe-stage glaucoma.
The odds of progression were higher for black (OR = 2.01, 95% CI: 1.61–2.49, P
= 3.91×10−10) and “other race” (OR = 1.66, 95% CI: 1.17–2.31, P = 0.003)
patients compared with white patients. Patients with private insurance had
lower odds of progression than those with public insurance (OR = 0.68, 95% CI:
0.55–0.85, P = 0.001), while patients with no listed insurance had no
significant difference compared with those with public insurance. Patients with
a history of one or more ophthalmic procedures had higher odds than those without
(OR = 1.81, 95% CI: 1.49–2.19, P = 1.54×10−9). AMD and RD diagnosis were
associated with increased odds of progression from early-stage to severe-stage
glaucoma (OR = 1.62, 95% CI: 1.13–2.26, P = 0.006; OR = 2.50, 95% CI:
1.57–3.85, P = 6.19×10−5). Finally, each additional prescribed glaucoma
medication was associated with 90% increased odds of progression (OR = 1.90,
95% CI: 1.80–2.00, P < 2×10−16).
Another
study was performed by Lin & colleagues, to compare the comorbid conditions
between open-angle glaucoma patients and a control cohort. [2] The study group
comprised of 76673 POAG patients, while the comparison group comprised of
230019 subjects matched to the study cohort. The data were collected
retrospectively from the Taiwan National Health Insurance Research Database. In
total, 31 medical comorbidities were selected based mainly on the Elixhauser
Comorbidity Index.
More
than half (50.5%) of the OAG patients had HT, and more than 30% had
hyperlipidemia or DM (30.5% and 30.2%, respectively). The prevalence of 28 of
31 comorbidities were significantly higher for OAG patients than subjects
without glaucoma after adjusting for age, gender, urbanization level, and
monthly income. The adjusted odds ratio was more than 1.50 for hypertension,
hyperlipidemia, systemic lupus erythematosus, diabetes, hypothyroidism, fluid
and electrolyte disorders, depression, and psychosis.
However,
a study by Motsko et al, did not find any association between glaucoma and
hypothyroidism. [3]
A
cross-sectional study of all glaucoma patients attending King AbdulAziz Medical
City in Saudi Arabia was performed by Talaat et al, to identify the
comorbidities in the patients.[4] A total of 283 patients met the inclusion
criteria. 61% of their sample had hypertension, which was much higher than
other reported studies from the region. Two mechanisms are postulated to
explain the relationship between hypertension and open-angle glaucoma. The
first is that increased arterial pressure will cause hardening and
atherosclerotic changes in the retinal vasculature with subsequent arteriolar
narrowing and elevated resistance, which eventually compromises the adequacy of
perfusion to the optic disc. The other mechanism is related to the use of
medications to lower blood pressure that might trigger episodes of systemic
hypotension, which results in transient reductions in ocular blood supply.
58%
individuals had DM. The mechanism by which DM is linked to glaucoma is believed
to arise from impaired autoregulation of retinal and elevated predilection of
retinal ganglion cells to programmed cell death.
Dyslipidemia
was seen in approximately 33.6% of the sample. This finding is similar to other
global studies but higher than local reports. there are reports of increased
risk of glaucoma in patients taking high doses of statin medications.
Diabetes
mellitus is not a well understood risk factor and its association to IOP or
POAG is still controversial.[5] The epidemiological studies remain
inconclusive, but some experimental studies have attempted to explain the biochemical
mechanisms that link both the diseases. Neurodegenerative mechanisms cause an
additional ganglion cell loss in glaucoma patients with DM. Therefore, the
already vulnerable ganglion cells in glaucoma eyes come under additional stress
in hyperglycemic conditions.
Large
population studies, such as the Beaver Dam study, Rotterdam study and the Blue
Mountains Eye study have shown an association between DM and higher IOP or
development of POAG. Similarly, Amstrong’s analysis of the incidence of
glaucoma in diabetes mellitus and a comparison with the incidence of glaucoma
in the general population showed two to three times higher incidence of
elevated IOP and POAG incidence in diabetes patients.[6] A recent meta-analysis
of 47 studies by Zhao and colleagues reported a pooled relative risk of
glaucoma of 1.48 in patients with diabetes compared to those without diabetes.
[7]
The
relationship between blood pressure (BP) and the incidence of glaucoma is still
being debated. Some studies report that there is no correlation between
systemic BP with IOP and the incidence of glaucoma. Even several other studies
reported that in younger patients, HTN gave a protective effect by increasing the
ocular perfusion pressure. However, some epidemiological studies have reported
that an increase in systemic BP is associated with a slight increase in IOP.
This is because the increase in BP increases episcleral venous pressure so that
the aqueous outflow will decrease, causing a proportional increase in IOP.
A
meta-analysis showed that individuals with systemic HTN had a significantly
1.71-fold risk of developing glaucoma compared with non-hypertensive
individuals (1.71 (95% CI 1.58 to 1.85)). [8]
High
BP can increase IOP through two mechanisms. First, an increase in the
production of aqueous humor, which is caused by an increase in capillary
pressure in the ciliary body, thereby increasing the intravascular pressure and
IOP gradient; second, decreasing the outflow of aqueous humor due to an
increase in episcleral venous pressure.
In
conclusion, most systemic co-morbidities increase the risk for POAG and such
patients should be monitored closely for the development/progression of
glaucoma.
REFERENCES:
[1]
Zhou, M. Y., Reed, H., Singh, R. P., Talcott, K. E., & Li, A. (2026).
Association Between Systemic Comorbidity Burden and Glaucoma Progression: A
5-Year Cohort Study. Journal of Glaucoma, 35(6),
386–392.
[2]
Lin HC, Chien CW, Hu CC, Ho JD. Comparison of comorbid conditions between
open-angle glaucoma patients and a control cohort: a case-control study.
Ophthalmology. 2010 Nov;117(11):2088-95.
[3]
Motsko SP, Jones JK. Is there an association between hypothyroidism and
open-angle glaucoma in an elderly population? An epidemiologic study.
Ophthalmology. 2008 Sep;115(9):1581-4.
[4]
Talaat K, Fathi OT, Alamoudi SM, Alzahrani MG, Mukhtar RM, Khan MA. Types of
Glaucoma and Associated Comorbidities Among Patients at King Abdulaziz Medical
City, Jeddah. Cureus. 2021 Jun 10;13(6):e15574.
[5]
Costa L, Cunha JP, Amado D, Pinto LA, Ferreira J. Diabetes Mellitus as a Risk
Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature
Review. J Curr Glaucoma Pract. 2015 Sep-Dec;9(3):81-5.
[6]
Armstrong JR, Daily RK, Dobson HL, Girard LJ. The incidence of glaucoma in
diabetes mellitus. A comparison with the incidence of glaucoma in the general
population. Am J Ophthalmol 1960 Jul;50:55-63.
[7]
Zhao D, Cho J, Kim MH, et al. Diabetes, fasting glucose, and the risk of
glaucoma: a meta-analysis. Ophthalmology. 2015; 122:72–8.
[8] Nislawati R, Taufik Fadillah Zainal A, Ismail A, et al. Role of hypertension as a risk factor for open-angle glaucoma:a systematic review and meta-analysis. BMJ Open Ophthalmology 2021;6:e000798. doi:10.1136/bmjophth-2021-000798.
